Metabolic dysfunction-associated fatty liver disease (MAFLD) is a significant global public health issue. Luteolin possesses several beneficial biological properties, including antioxidation and anti-inflammation. This study investigated luteolin’s effect and potential mechanisms on MAFLD in high-fat diet (HFD)-fed rats. Rats were administered an HFD supplemented with fructose for 12 weeks to induce MAFLD. After that, the HFD-fed rats were given either luteolin (50 or 100 mg/kg/day) or metformin (100 mg/kg/day) for 4 weeks. Luteolin improved metabolic parameters induced by the HFD, since it decreased body weight, blood pressure, fasting blood glucose, serum insulin, free fatty acids, cholesterol, and triglyceride levels (p < 0.05). Luteolin reduced hepatic injury and inflammatory markers in HFD-fed rats (p < 0.05). Additionally, HFD-fed rats treated with luteolin showed reduced malondialdehyde and raised catalase activity in plasma (p < 0.05). Luteolin attenuated hepatic steatosis compared to the untreated rats (p < 0.05). Luteolin also increased plasma adiponectin levels accompanied by upregulation of adiponectin receptor 1 (AdipoR1), AMP-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor γ (PPAR-γ) protein expression in liver (p < 0.05). These findings revealed that luteolin ameliorated HFD-induced MAFLD in rats, possibly by reducing metabolic alterations and oxidative stress and restoring AdipoR1, AMPK, and PPARγ protein expression in HFD-fed rats.

Maternal obesity has been shown to impair the oxidative status in the placenta and newborns, potentially leading to adverse pregnancy outcomes and long-term effects on the programming of offspring metabolic status. This study aimed to investigate the impact of maternal obesity on maternal and umbilical cord plasma oxidative status, as well as placental oxidative adaptation. Maternal obesity (n = 20), defined as a pre-pregnancy BMI ≥ 25 kg/m², and maternal leanness (n = 20), defined as a pre-pregnancy BMI < 23 kg/m², were the group categories used in this study. Both groups were matched according to gestational age at delivery. Maternal blood, umbilical cord blood, and placental tissue were collected to assess nutritional content (cholesterol, triglyceride, and protein), oxidative stress markers (MDA and protein carbonyl), and antioxidant activity (SOD and catalase). Placental protein expression (SOD2, catalase, UCP2, and Nrf2) was evaluated using Western blot analysis. Catalase activity in maternal plasma significantly increased in the maternal obesity group (p = 0.0200), with a trend toward increased MDA and protein carbonyl levels. In umbilical cord plasma, triglyceride, protein carbonyl, and catalase activity were significantly elevated in the maternal obesity group compared with the lean controls (p = 0.0482, 0.0291, and 0.0347, respectively). Placental protein expression analysis revealed significantly decreased SOD2 (p = 0.0011) and catalase (p < 0.0001), along with Nrf2 downregulation (p < 0.0001). An increase in mitochondrial antioxidant UCP2 expression was observed (p = 0.0117). The neonatal protein carbonyl levels positively correlated with placental protein carbonyl (r = 0.7405, p < 0.0001) and negatively correlated with maternal catalase activity (r = −0.4332, p = 0.0052). This study thus provides evidence that maternal obesity is associated with placental and fetal oxidative stress, alongside a concurrent increase in placental antioxidant UCP2 expression.

Background. Kaempferol is a natural flavonoid with a wide range of pharmacological effects. The current study tested whether kaempferol prevents hypertension‐induced renal remodelling in rats. During the 5 weeks of experiments, rats (n = 7/group) were administered N_ω‐nitro‐L‐arginine methyl ester hydrochloride (L‐NAME) (40 mg/kg/day) with either vehicle or kaempferol (20 mg/kg/day) or kaempferol (40 mg/kg/day) or lisinopril (5 mg/kg/day). Results. Kaempferol treatment alleviated haemodynamic changes occurring in hypertensive rats, including increases in systolic and diastolic blood pressure, pulse pressure, mean arterial pressure, and heart rate (p < 0.05). Kaempferol treatment prevented glomerular hypertrophy by reducing the increased glomerular cross‐sectional area, glomerular tuft area, Bowman’s space area, glomerular volume, and the extent of renal tubulointerstitial fibrosis induced by hypertension (p < 0.05). Furthermore, animals in the L‐NAME group showed elevated angiotensin‐converting enzyme (ACE) activity and angiotensin II (Ang II) levels compared to those in the kaempferol‐treated group (p < 0.05). Kaempferol treatment also reverted the elevations in levels of superoxide anions and malondialdehyde and reduced catalase and superoxide dismutase activity in hypertensive rats (p < 0.05). L‐NAME‐treated rats showed overexpression of angiotensin II receptor type 1 (AT1), nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), and matrix metalloproteinase‐9 (MMP‐9) proteins; conversely, the expression of these proteins was reduced in the kaempferol‐treated group (p < 0.05). Conclusion. Kaempferol treatment alleviated renal remodelling induced in rats by chronic hypertension. These mechanisms may be associated with the inhibition of ACE activity and suppression of the Ang II/AT1 receptor/NOX4/MMP‐9 cell signalling pathway in renal tissue.

Maternal obesity has been found to be impaired oxidative status in placenta and newborn which can lead to adverse pregnancy outcomes and long-term adverse influence on metabolic programming in the offspring. This study aimed to investigate the role of maternal obesity on maternal and umbilical cord plasma oxidative status and placental oxidative adaptation. Maternal obesity (n=20) defined as pre-pregnancy BMI ≥ 25 kg/m² and maternal lean (n=20) defined as pre-pregnancy BMI < 25 kg/m² were recruited into this study. Both groups were matched by gestational age at delivery. Maternal blood, umbilical cord blood and placental tissue were collected to assess nutritional content (cholesterol, triglyceride, and protein), oxidative stress marker (MDA and protein carbonyl) and antioxidant activity (SOD and catalase). Placenta protein expression (SOD2, catalase, UCP2 and Nrf2) was evaluated by western blot analysis. Catalase activity in maternal plasma significantly increased in maternal obesity group (p = 0.0200) with an increased trend in MDA and protein carbonyl levels. Umbilical cord plasma triglyceride, protein carbonyl and catalase activity significantly increased in maternal obesity compared with that in maternal lean (p = 0.0462, 0.0485, and 0.0348, respectively). Although placenta protein expression analysis exhibited significant decreased SOD2 (p = 0.0169) and catalase (p = 0.0067), accompanied by Nrf2 downregulation (p = 0.0453). An increased mitochondrial antioxidant UCP2 expressions was observed (p = 0.0143). Hence, our study provided evidence that maternal obesity is associated with placental and fetal oxidative stress with the parallel increased placental antioxidant UCP2 expression.

This study aimed to examine the potential effects and mechanisms of diosmin, a flavone glycoside, on blood pressure and cardiovascular abnormalities in a rat model of hypertension caused by renal artery stenosis. Male Sprague-Dawley rats were operated on two-kidney, one-clip (2K-1C) to induce renovascular hypertension. Following three weeks of surgery, 2K-1C rats were subjected to daily oral administration of diosmin (25 or 50 mg/kg) or telmisartan (5 mg/kg) for four weeks. Diosmin significantly reduced blood pressure and enhanced left ventricular (LV) performance and vascular endothelial function (P < .05). Diosmin also diminished left ventricular and aortic remodeling. It dramatically decreased oxidative stress markers, enhancing antioxidant enzyme activity, and nitric oxide metabolite levels (P < .05). Diosmin reduced the indicators of the classical renin-angiotensin system (RAS) while augmenting the indicators of the non-classical RAS. Diosmin modulated the expression of angiotensin II type 1 receptor (AT1R), angiotensin II type 1 receptor, Mas receptor (MasR), and matrix metalloproteinase-9 in cardiac tissue (P < .05). Telmisartan exhibited effects comparable to those of diosmin. Molecular docking indicated that AT1R may serve as a molecular target for diosmetin, a metabolite of diosmin; nonetheless, its affinity was lower to that of telmisartan. In conclusion, diosmin markedly decreased blood pressure and enhanced cardiovascular function and remodeling, likely through the modulation of RAS and the attenuation of oxidative stress in 2K-1C hypertensive rats.

Excessive high-fat diet (HFD) intake can precipitate metabolic dysfunction-associated fatty liver disease (MAFLD). Tangeretin is a citrus flavonoid possessing many biological properties. We examined the impact of tangeretin on MAFLD and its underlying mechanism. Rats were given HFD plus 15% fructose solution for four months to produce metabolic syndrome. Metabolic syndrome rats were administered 100 mg/kg of metformin or 25 mg/kg of tangeretin for the last four weeks. HFD-induced increased body weight, liver weight, adipose tissue weight, fasting blood glucose, serum insulin, total triglyceride, total cholesterol, and free fatty acids and reduced adiponectin and high-density lipoprotein cholesterol levels in metabolic syndrome, which were alleviated by tangeretin (p < 0.05). Tangeretin stabilized alanine transaminase activity, liver catalase, and inflammatory and oxidative stress markers in HFD rats compared to untreated HFD rats (p < 0.05). Tangeretin reduced hepatic steatosis induced by HFD. Downregulation of hepatic insulin receptor substrate-1 (IRS-1) and protein kinase B (Akt) protein expression in metabolic syndrome rats was recovered by tangeretin (p < 0.05). Metformin, an antihyperglycemic drug, produced comparable effects to tangeretin. In conclusion, tangeretin attenuates metabolic disorders and fatty liver induced by HFD in rats. The underlying mechanisms involve reducing oxidative stress, and inflammation and enhancing insulin sensitivity.